Journal article
Noninvasive molecular imaging of the enhanced permeability and retention effect by64Cu-liposomes: In vivo correlations with68Ga-RGD, fluid pressure, diffusivity and18F-FDG
University of Copenhagen1
Department of Health Technology, Technical University of Denmark2
Biotherapeutic Engineering and Drug Targeting, Department of Health Technology, Technical University of Denmark3
Colloids & Biological Interfaces, Biotherapeutic Engineering and Drug Targeting, Department of Health Technology, Technical University of Denmark4
Background: The accumulation of liposome encapsulated chemotherapy in solid cancers is dependent on the presence of the enhanced permeability and retention (EPR) effect. Positron emission tomography (PET) imaging with a liposome encapsulated radioisotope, such as liposome encapsulated Cu-64 (64Cu-liposome) may help to identify tumors with high lipo-some accumulation, and thereby stratify patients based on expected benefit from liposomal chemotherapy.
However, intravenous administration of liposomes without a cytotoxic con-tent is complicated by the accelerated blood clearance (ABC) phenomenon for succeeding therapeutic liposome dosing. Alternative markers for assessing the tumor’s EPR level are therefore warranted. Materials and Methods: To increase our understanding of EPR variations and to ulti-mately identify an alternative marker for the EPR effect, we investigated the correlation between64Cu-liposome PET/CT (EPR effect) and68Ga-RGD PET/CT (neoangiogenesis),18F-FDG PET/CT (glycolysis), diffusion-weighted MRI (diffusivity) and interstitial fluid pressure in two experimental cancer models (CT26 and COLO 205).
Results:64Cu-liposome and68Ga-RGD SUVmax displayed a significant moderate correla-tion, however, none of the other parameters evaluated displayed significant correlations. These results indicate that differences in neoangiogenesis may explain some EPR variability, however, as correlations were only moderate and not observed for SUVmean,68Ga-RGD is probably insufficient to serve as a stand-alone surrogate marker for quantifying the EPR effect and stratifying patients.
Language: | English |
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Publisher: | Dove |
Year: | 2020 |
Pages: | 8571-8581 |
ISSN: | 11782013 and 11769114 |
Types: | Journal article |
DOI: | 10.2147/IJN.S239172 |
ORCIDs: | Elema, Dennis Ringkjøbing , 0000-0002-2706-5547 , Henriksen, Jonas Rosager , Andresen, Thomas Lars and 0000-0002-0285-024X |
EPR effect Liposome Neoangiogenesis Positron emission tomography SDG 3 - Good Health and Well-being
Animals Cell Line, Tumor Colorectal Neoplasms Contrast Media Copper Radioisotopes Copper-64 Diffusion Female Fluorodeoxyglucose F18 Gallium Radioisotopes Gallium-68 Humans Liposomes Magnetic Resonance Imaging Mice, Inbred BALB C Molecular Imaging Neoplasms Neovascularization, Pathologic Oligopeptides Permeability Positron Emission Tomography Computed Tomography Pressure Radiopharmaceuticals Tumor Microenvironment Xenograft Model Antitumor Assays arginyl-glycyl-aspartic acid liposome neoangiogenesis positron emission tomography